Asymmetric Addition of Aldehydes and Ketones to Chiral 2-Azapentadienyl Lithium Compounds: Diastereoselective Synthesis of 4-Vinyl-4,5-dihydro-oxazoles

Abstract

Chiral 2-azapentadienyl lithium compounds 1, easily available by deprotonation of the corresponding N-allylimines 2, react with symmetrical and asymmetrical ketones and aldehydes to form new chiral, vinyl-substituted 4,5-dihydro-oxazoles 3. The structural properties of 1 in the gas phase and in solution were studied by quantum chemical calculations and NMR spectroscopy. The X-ray diffraction structure of 4,5-dihydro-oxazole 3d indicates the formation of a benzhydrol adduct. The new reactions are interpreted in terms of regioselective, stepwise additions of the carbonyl compounds to carbon atom C3 of 1 and subsequent removal of the chiral nucleofugal group.

Key words

addition reactions - asymmetric synthesis - chiral 2-azapentadienyl lithium compounds - chiral 4,5-dihydro-oxazoles - heterocycles

References

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  We are very grateful to Dr. J. Harbach, research group of Prof. Dr. H. Ahlbrecht at the organic institute of the University of Giessen, Germany, for conducting the cryoscopic measurements.

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Gaussian 98, Revision A.6 Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, Jr., J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone,V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian, Inc., Pittsburgh PA, 1998.

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Details of the quantum chemical calculations (GAUSSIAN 98 archive entries) may be obtained from E.-U.W. upon request.

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Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-151211. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (Fax:[phone]; E-mail: [e-mail]).

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Programs used: Data collection: Express; Nonius B. V., 1994.- Data reduction: MolEN: Fair, K. Enraf-Nonius B. V., 1990. - Structure solution: SHELXS-86 and SHELXS-97: Sheldrick, G. M. Acta Crystallogr., Sect. A 1990, 46, 467-473.- Structure refinement: SHELXL-97: Sheldrick, G. M. Universität Göttingen, 1997. - Graphics: SCHAKAL: Keller, E. Universität Freiburg, 1997.